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Otitis media peptide

Arwa Kurabi, Daniel Schaerer, Lisa Chang, Kwang Pak, Allen F Ryan
Local treatment of middle ear (ME) disease currently requires surgical penetration of the tympanic membrane (TM). We previously discovered 12-mer peptides that are actively transported across the intact TM, a process that could be used for non-invasive drug delivery into the ME. To optimise transport and provide further understanding of the peptides transport mechanism, we extended two of the candidate peptides by six additional amino acids at random, and screened the resulting 18-mers libraries on TMs of rats with active bacterial otitis media (OM) for transport efficiency using phage display...
August 16, 2017: Journal of Drug Targeting
Chung Man Sung, Hong Chan Kim, Yong Beom Cho, Song Yub Shin, Chul Ho Jang
INTRODUCTION: Methicillin-Resistant Staphylococcus aureus (MRSA) is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat MRSA otorrhea. OBJECTIVE: In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it applied topically in the middle ear of guinea pigs. METHODS: The antimicrobial activity of KR-12-a2 against MRSA strains was examined by using the inhibition zone test...
May 31, 2017: Brazilian Journal of Otorhinolaryngology
Majela González-Miro, Laura Rodríguez-Noda, Mildrey Fariñas-Medina, Dagmar García-Rivera, Vicente Vérez-Bencomo, Bernd H A Rehm
Streptococcus pneumoniae is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens...
April 2017: Heliyon
Timothy F Murphy, Aimee L Brauer, Antoinette Johnson, Charmaine Kirkham
Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media (middle ear infections) in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. In view of the huge global burden of disease caused by M. catarrhalis, the development of vaccines to prevent these infections and better approaches to treatment have become priorities. In previous work, we used a genome mining approach that identified three substrate binding proteins (SBPs) of ATP-binding cassette (ABC) transporters as promising candidate vaccine antigens...
2016: PloS One
Stephanie Val, Marian Poley, Kristy Brown, Rachel Choi, Stephanie Jeong, Annie Colberg-Poley, Mary C Rose, Karuna C Panchapakesan, Joe C Devaney, Marcos Perez-Losada, Diego Preciado
BACKGROUND: Chronic Otitis Media (COM) is characterized by middle ear effusion (MEE) and conductive hearing loss. MEE reflect mucus hypersecretion, but global proteomic profiling of the mucosal components are limited. OBJECTIVE: This study aimed at characterizing the proteome of MEEs from children with COM with the goal of elucidating important innate immune responses. METHOD: MEEs were collected from children (n = 49) with COM undergoing myringotomy...
2016: PloS One
Arwa Kurabi, Kwang K Pak, Marlen Bernhardt, Andrew Baird, Allen F Ryan
Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. While local treatment would avoid the systemic treatment side-effects, the tympanic membrane (TM) represents an impenetrable barrier unless surgically breached. We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. We used two M13-bacteriophage display biopanning strategies to search for mediators of trans-TM transport. First, aliquots of linear phage library displaying 10(10th) 12mer peptides were applied on the TM of rats with active bacterial OM...
March 7, 2016: Scientific Reports
Arun Sharma, Pooja Gupta, Rakesh Kumar, Anshu Bhardwaj
Increasingly, biofilms are being recognised for their causative role in persistent infections (like cystic fibrosis, otitis media, diabetic foot ulcers) and nosocomial diseases (biofilm-infected vascular catheters, implants and prosthetics). Given the clinical relevance of biofilms and their recalcitrance to conventional antibiotics, it is imperative that alternative therapeutics are proactively sought. We have developed dPABBs, a web server that facilitates the prediction and design of anti-biofilm peptides...
February 25, 2016: Scientific Reports
Gehad M Yassin, Magdy A Amin, Ahmed S Attia
BACKGROUND: Moraxella catarrhalis is an established pathogen that is causing substantial infections to both children and adults. However, so far there is no effective vaccine to halt the spread of these infections. METHODS: Immunoinformatics tools were used to predict M. catarrhalis epitopes that could offer immunoprotection among major proportions of human populations worldwide. Mice were immunized with the best 3 peptides and then challenged with M. catarrhalis in the pulmonary clearance model...
June 15, 2016: Journal of Infectious Diseases
Chun-Zhen Hua, Wei-Lin Hu, Shi-Qiang Shang, Jian-Ping Li, Li-Quan Hong, Jie Yan
Nontypeable Haemophilus influenzae (NTHi) is one of the most common etiologies of acute otitis media, rhinosinusitis, and pneumonia. Outer membrane proteins (OMPs) are the main focus in new vaccine development against NTHi, as the H. influenzae type b (Hib) vaccine does not cover noncapsulated NTHi. The OMPs P6 and protein D are the most promising candidate antigens for an NTHi vaccine, and low antibody levels against them in serum may be correlated with infection caused by NTHi. In the current study, we measured the antibody titers against P6, protein D, and their T- and B-cell combined peptide epitopes in healthy individuals of different ages...
December 16, 2015: Clinical and Vaccine Immunology: CVI
Masaki Ikeda, Noriyuki Enomoto, Dai Hashimoto, Tomoyuki Fujisawa, Naoki Inui, Yutaro Nakamura, Takafumi Suda, Toshi Nagata
BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is one of the most common Gram-negative pathogens in otitis media and exacerbation of chronic obstructive pulmonary disease. NTHi has been reported to invade bronchial epithelial cells. This penetration enables NTHi to evade the host immune system and antibiotics, and it seems to be related to the intractable features of these diseases. However, the precise mechanism of the invasion has been unknown. We hypothesized that protein-E, an outer membrane protein of NTHi, plays a role in this penetration into bronchial epithelial cells...
2015: BMC Microbiology
Paul W Whitby, Thomas W Seale, Daniel J Morton, Terrence L Stull
Nontypeable Haemophilus influenzae (NTHi) cause significant disease, including otitis media in children, exacerbations of chronic obstructive pulmonary disease, and invasive disease in susceptible populations. No vaccine is currently available to prevent NTHi disease. The interactions of NTHi and the human host are primarily mediated by lipooligosaccharide and a complex array of surface-exposed proteins (SEPs) that act as receptors, sensors and secretion systems. We hypothesized that certain SEPs are present in all NTHi strains and that a subset of these may be antibody accessible and represent protective epitopes...
2015: PloS One
Megan M Jones, Timothy F Murphy
Moraxella catarrhalis causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. Together, these two conditions contribute to enormous morbidity and mortality worldwide. The oligopeptide permease (opp) ABC transport system is a nutritional virulence factor important for the utilization of peptides. The substrate binding protein OppA, which binds peptides for uptake, is a potential vaccine antigen, but little was known about the regulation of gene expression. The five opp genes oppB, oppC, oppD, oppF, and oppA are in the same open reading frame...
September 2015: Infection and Immunity
Deborah M B Post, Jason M Held, Margaret R Ketterer, Nancy J Phillips, Alexandria Sahu, Michael A Apicella, Bradford W Gibson
BACKGROUND: Non-typeable H. influenzae (NTHi) is a nasopharyngeal commensal that can become an opportunistic pathogen causing infections such as otitis media, pneumonia, and bronchitis. NTHi is known to form biofilms. Resistance of bacterial biofilms to clearance by host defense mechanisms and antibiotic treatments is well-established. In the current study, we used stable isotope labeling by amino acids in cell culture (SILAC) to compare the proteomic profiles of NTHi biofilm and planktonic organisms...
December 31, 2014: BMC Microbiology
Megan M Jones, Antoinette Johnson, Mary Koszelak-Rosenblum, Charmaine Kirkham, Aimee L Brauer, Michael G Malkowski, Timothy F Murphy
Moraxella catarrhalis is a strict human pathogen that causes otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, resulting in significant worldwide morbidity and mortality. M. catarrhalis has a growth requirement for arginine; thus, acquiring arginine is important for fitness and survival. M. catarrhalis has a putative oligopeptide permease ABC transport operon (opp) consisting of five genes (oppB, oppC, oppD, oppF, and oppA), encoding two permeases, two ATPases, and a substrate binding protein...
November 2014: Infection and Immunity
Nidia León-Sicairos, Uriel A Angulo-Zamudio, Jorge E Vidal, Cynthia A López-Torres, Jan G M Bolscher, Kamran Nazmi, Ruth Reyes-Cortes, Magda Reyes-López, Mireya de la Garza, Adrian Canizalez-Román
Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million child deaths annually. Pneumococcus causes infections such as pneumonia, otitis media, meningitis, and sepsis. The human immune system includes antibacterial peptides and proteins such as lactoferrin (LF), but its activity against pneumococcus is not fully understood. The aim of this work was to evaluate the bactericidal effect of bovine lactoferrin (bLF) and the synthetic LF-peptides lactoferricin (LFcin17-30), lactoferrampin (LFampin265-284), and LFchimera against S...
October 2014: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Eric A Jones, Anchasa Kananurak, Charles L Bevins, Edward J Hollox, Lauren O Bakaletz
As there is increasing evidence that aberrant defensin expression is related to susceptibility for infectious disease and inflammatory disorders, we sought to determine if copy number of the beta-defensin gene cluster located on chromosome 8p23.1 (DEFB107, 106, 105, 104, 103, DEFB4 and SPAG11), that shows copy number variation as a block, was associated with susceptibility to otitis media (OM). The gene DEFB103 within this complex encodes human beta defensin-3 (hBD-3), an antimicrobial peptide (AP) expressed by epithelial cells that line the mammalian airway, important for defense of mucosal surfaces and previously shown to have bactericidal activity in vitro against multiple human pathogens, including the three that predominate in OM...
2014: PloS One
Jeong-Im Woo, Sung-Hee Kil, Douglas E Brough, Yoo Jin Lee, David J Lim, Sung K Moon
Otitis media (OM), one of the most prevalent diseases in young children, is clinically important owing to its high incidence in children and its potential impact on language development and motor coordination. OM is the most common reason for the prescription of antibiotics (accounting for 25% of prescriptions) due to its extremely high incidence. A recent increase in antibiotic resistance among OM pathogens is emerging as a major public health concern globally, which led us to consider non-antibiotic approaches for the management of OM...
February 2015: Innate Immunity
Nathan C LaCross, Carl F Marrs, Janet R Gilsdorf
Nontypeable Haemophilus influenzae (NTHi) colonize the human pharynx asymptomatically, and are also an important cause of otitis media (OM). Previous studies have demonstrated that some genes are more prevalent in OM-causing NTHi strains than in commensal strains, suggesting a role in virulence. These studies, however, are unable to investigate the possible associations between gene polymorphisms and disease. This study examined amino acid polymorphisms and sequence diversity in a potential virulence gene, the hemin receptor hemR, from a previously characterized NTHi strain collection containing both commensal and OM organisms to identify possible associations between the polymorphisms and otitis media...
August 2014: Infection, Genetics and Evolution
Marcus Wessman, Thomas Bjarnsholt, Steffen Robert Eickhardt-Sørensen, Helle Krogh Johansen, Preben Homøe
The objectives of this study were to examine middle ear biopsies from Greenlandic patients with chronic otitis media (COM) for the presence of mucosal biofilms and the bacteria within the biofilms. Thirty-five middle ear biopsies were obtained from 32 Greenlandic COM patients admitted to ear surgery. All biopsies were examined by means of peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH), and if possible culture and polymerase chain reaction (PCR) of the 16s rDNA and sequencing. Light microscopy and confocal laser scanning microscopy were used...
May 2015: European Archives of Oto-rhino-laryngology
Beth Mann, Justin Thornton, Richard Heath, Kristin R Wade, Rodney K Tweten, Geli Gao, Karim El Kasmi, John B Jordan, Diana M Mitrea, Richard Kriwacki, Jeff Maisonneuve, Mark Alderson, Elaine I Tuomanen
BACKGROUND:  Pneumococcus, meningococcus, and Haemophilus influenzae cause a similar spectrum of infections in the ear, lung, blood, and brain. They share cross-reactive antigens that bind to the laminin receptor of the blood-brain barrier as a molecular basis for neurotropism, and this step in pathogenesis was addressed in vaccine design. METHODS:  Biologically active peptides derived from choline-binding protein A (CbpA) of pneumococcus were identified and then genetically fused to L460D pneumolysoid...
April 1, 2014: Journal of Infectious Diseases
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